GeneBe

SARS1

protein-coding

seryl-tRNA synthetase 1, the group of Aminoacyl tRNA synthetases, Class II

Gene summary

This gene belongs to the class II amino-acyl tRNA family. The encoded enzyme catalyzes the transfer of L-serine to tRNA (Ser) and is related to bacterial and yeast counterparts. Multiple alternatively spliced transcript variants have been described but the biological validity of all variants is unknown. [provided by RefSeq, Jul 2010]

Previous symbols:
  • SARS

MANE transcript

NM_006513.4

Inheritance

AR, AD

ClinVar variants

P:2U:64B:14

Top phenotype

Neurodevelopmental disorder with microcephaly, ataxia, and seizures

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr1:109,213,918-109,238,182

External References & Databases

Ensembl (ENSG00000031698)NCBI Gene (6301)OMIM (607529)HGNC:10537GenCCUniProt (P49591)AlphaFoldClinVar (SARS1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~24.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with microcephaly, ataxia, and seizuresLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0060577

Submitter: ClinGen

SARS1 was first reported in relation to autosomal recessive neurodevelopmental disorder with microcephaly, ataxia, and seizures in 2017 (Musante et al., PMID: 28236339). Five missense variants, reported in 6 probands in 4 publications (PMIDs: 28236339, 34570399, 36004946, 35790048) are included in this curation. Variants in this gene have also been reported segregating with disease (PMIDs: 28236339, 34570399). The mechanism of pathogenicity is reported to be loss of function. In summary, there is limited evidence to support the relationship between SARS1 and autosomal recessive neurodevelopmental disorder with microcephaly, ataxia, and seizures. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on July 18, 2023 (SOP Version 9).

autosomal recessive non-syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019502

Submitter: Orphanet

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

hereditary peripheral neuropathySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0020127

Submitter: PanelApp Australia

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

neurodevelopmental disorder with microcephaly, ataxia, and seizuresMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0060577

Submitter: G2P

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with microcephaly, ataxia, and seizuresAR

Manifestation: Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 28236339Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SARS1 variants in ClinVar

8 Conditions Cataloged
not specifiedTotal: 54
not providedTotal: 12
Neurodevelopmental disorder with microcephaly, ataxia, and seizuresTotal: 12
SARS1-related disorderTotal: 5
Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndromeTotal: 2
Hereditary peripheral neuropathyTotal: 1
Cerebral arteriovenous malformationTotal: 1
See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006513.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
10
clinvar
2
clinvar
 14
missense
1
clinvar
58
clinvar
2
clinvar
 61
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
1
clinvar
3
clinvar
 4
Total116412280

Highest pathogenic variant AF is 0.000006840441

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_006513.4RefSeqNP_006504.211MANE Select
ENST00000234677.7EnsemblENSP00000234677.211MANE Select
NM_001330669.1RefSeqNP_001317598.112Standard
ENST00000369923.4EnsemblENSP00000358939.412Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
sarsDanio rerio

Structure: trunk vasculature

Quality: branchiness

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Aminoacyl-tRNA biosynthesis - Homo sapiens (human)
  • 3-Phosphoglycerate dehydrogenase deficiency
  • Non Ketotic Hyperglycinemia
  • Glycine and Serine Metabolism
  • Dimethylglycine Dehydrogenase Deficiency

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • translation
  • tRNA aminoacylation for protein translation
  • seryl-tRNA aminoacylation
  • tRNA processing

Molecular Function

  • RNA polymerase II proximal promoter sequence-specific DNA binding
  • RNA binding
  • serine-tRNA ligase activity
  • protein binding
  • ATP binding

Cellular Component

  • nucleus
  • cytoplasm
  • cytosol
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000234677
Coding exons
11
Length
24252
Individuals with no LoFs
125744
Homozygous LoFs
0
Heterozygous LoFs
3
Defined
125747
p
0.0000119
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.661702990.5680.00001703378
Missense (PolyPhen)36114.750.313721309
Synonymous1.48941140.8230.00000639973
Loss of Function4.70229.60.06750.00000175321

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser- AMP and then transferred to the acceptor end of tRNA(Ser) (PubMed:22353712, PubMed:24095058, PubMed:9431993, PubMed:26433229, PubMed:28236339). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) (PubMed:9431993, PubMed:26433229, PubMed:28236339). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC (PubMed:24940000). Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA (PubMed:19423848, PubMed:19423847, PubMed:24940000). {ECO:0000269|PubMed:19423847, ECO:0000269|PubMed:19423848, ECO:0000269|PubMed:22353712, ECO:0000269|PubMed:24095058, ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:26433229, ECO:0000269|PubMed:28236339, ECO:0000269|PubMed:9431993}.;
Disease
DISEASE: Neurodevelopmental disorder with microcephaly, ataxia, and seizures (NEDMAS) [MIM:617709]: An autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, seizures apparent in infancy, impaired speech, and aggressive behavior. Additional features include microcephaly, ataxia, and muscle weakness. {ECO:0000269|PubMed:28236339}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.261

Intolerance Scores

LoFtool
0.145
RVIS EVS
-0.32
RVIS percentile EVS
31.69

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.999

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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